Objective:To explore the pathogenicity and genotype-phenotype correlation of a c. 158G>A variant of phenylalanine hydroxylase ( PAH) gene among patients with PAH deficiency. Methods:Thirty seven children diagnosed with PAH deficiency at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University between July 2016 and June 2021 were selected as the study subjects. Clinical data and results of genetic testing were retrospectively analyzed.Results:Among the 37 patients, mild hyperphenylalaninemia (HPA) was observed in 34 cases, two PAH variants (including c. 158G>A), which formed a compound heterozygous mutation genotype, were detected in 33 patients, and the remainder one was found to harbor three PAH variants, including homozygous c. 158G>A variants and a heterozygous c. 842+ 2T>A variant. Classical phenylketonuria (PKU) was observed in 3 patients, and three PAH variants were detected in each of them, including two with c. [158G>A, 842+ 2T>A]/c.728G>A and c. [158G>A, 842+ 2T>A]/c.611A>G, respectively, and one with c. [158G>A, c. 722G>A]/c.728G>A. The c. 158G>A variant has a minimal influence on the PAH activity and is associated with a mild HPA phenotype. The variant should thereby be classified as likely benign. Conclusion:When the c. 158G>A variant and other pathogenic variants are arranged in cis position, the ultimate phenotype will be determined by the pathogenicity of other variants.

Laboratory animal science plays a crucial role in the education and training of medical students.To ensure effective teaching of laboratory animal science in Chinese medicine institutions,the principles of Chinese medicine characteristics and innovation should be incorporated.This pedagogical approach aims to enrich traditional cultural literacy in Chinese medicine and foster the students'capacities for innovation and critical thinking.Daily teaching of laboratory animal science should encompass various educational aspects,including inheritance,ethics,migration,exploration,inspiration,and extension education.By integrating these components and emphasizing the intersections of Chinese medicine with laboratory animal science,important areas,such as animal welfare in Chinese medicine research,the application of Chinese medicine theories in animal experiments,considerations for animal models in Chinese medicine,and the selection of experimental animal species,can be addressed.Additionally,this approach guides new research directions and effectively cultivates the students'scientific research,innovation,and practical abilities.The primary objective of this program is to nurture scientific innovation and practical competence among students while prioritizing the superior quality of innovative education in the context of Chinese medicine.Such efforts offer a solid foundation to advance traditional medical practices and nurture a new generation of professionals dedicated to preserving traditional medicine.

Objective:To preliminarily investigate the effect of blue light on the biological activity of human skin keratinocytes, fibroblasts and melanocytes.Methods:Discarded foreskin tissues were collected from 10 healthy children aged from 3 to 12 years after circumcision surgery in the First Affiliated Hospital of Kunming Medical University from June 2021 to December 2021. After epidermis-dermis separation, selective culture was performed to isolate keratinocytes, fibroblasts, and melanocytes. According to the pre-experiment results, the above three types of cells were irradiated with 440 - 450 nm blue light at doses of 0, 5, 10, 20, 30, and 40 J/cm 2, and then continued to be cultured for 0, 6, 24, and 48 hours. Cell counting kit 8 (CCK8) assay was performed to evaluate cellular proliferative activity at each time point, enzyme-linked immunosorbent assay (ELISA) to detect levels of interleukin (IL) -18, IL-33, nerve growth factor (NGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by keratinocytes, as well as levels of IL-33 and keratinocyte growth factor (KGF) secreted by fibroblasts, NaOH lysis method to determine melanin synthesis rates in melanocytes, and Western blot analysis to determine the relative expression of tyrosinase (TYR), tyrosine-related protease 1 (TRP-1) and dopachrome isomerase (DCT) in melanocytes. Two-way analysis of variance was used to analyze group effects, time effects and interaction effects. Results:After irradiation with blue light, the cellular proliferative activity significantly differed among different doses of blue light irradiation groups and different time points in keratinocytes ( Ftime = 516.20, Fdose = 421.20, Finteraction = 25.05, all P < 0.003), fibroblasts ( Ftime = 129.30, Fdose = 477.80, Finteraction = 10.91, all P < 0.003), and melanocytes ( Ftime = 77.61, Fdose = 138.70, Finteraction = 3.50, all P < 0.003) ; immediately after irradiation, the proliferative activity of keratinocytes and fibroblasts was significantly lower in the 20 - 40 J/cm 2 blue light group than in the 0 J/cm 2 blue light group (all P < 0.003), and the proliferative activity of melanocytes was significantly higher in the 5 J/cm 2 blue light group than in the 0 J/cm 2 blue light group ( P < 0.003) ; the proliferative activity of the 3 types of cells showed decreasing trends with the increase of blue light irradiation doses and culture time. ELISA showed that the concentrations of IL-18, IL-33, NGF, and GM-CSF secreted by keratinocytes, as well as the concentrations of IL-33 and KGF secreted by fibroblasts, tended to increase with the increase of blue light irradiation doses and culture time. The melanin synthesis rates in melanocytes significantly differed among different doses of blue light irradiation groups and different time points ( Ftime = 833.50, Fdose = 249.40, Finteraction = 81.38, all P < 0.003) ; during 0 - 24 hours after blue light irradiation, the melanin synthesis rates tended to increase with the increase of blue light irradiation doses and time; during 24 - 48 hours, the melanin synthesis rates showed decreasing trends with the increase of blue light irradiation doses and culture time compared with that at 24 hours after irradiation; 24 hours after irradiation, the melanin synthesis rates were significantly higher in the 5, 10, 20, 30 and 40 J/cm 2 blue light groups (159.50% ± 10.88%, 218.76% ± 8.49%, 333.72% ± 7.72%, 393.29% ± 6.00%, 427.21% ± 8.39%, respectively) than in the 0 J/cm 2 blue light group (102.29% ± 6.57%, all P < 0.003). The relative expression of TYR ( Ftime = 67.94, Fdose = 28.99, Finteraction = 3.71, all P < 0.003), TRP-1 ( Ftime = 21.73, Fdose = 8.38, both P < 0.003) and DCT ( Ftime = 34.51, Fdose = 11.79, both P < 0.003) in melanocytes significantly differed among different doses of blue light irradiation groups and different time points, and tended to increase with the increase of blue light irradiation doses and culture time. Conclusion:Blue light irradiation at doses of 5 - 40 J/cm 2 could inhibit the proliferative activity of human skin keratinocytes, fibroblasts, and melanocytes, and the inhibitory effect tended to increase with the increase of blue light irradiation doses, except an enhancing effect on the proliferative activity of melanocytes observed immediately after irradiation with blue light at 5 J/cm 2; additionally, blue light irradiation at 5 - 40 J/cm 2 could enhance the expression of melanin synthesis-related enzymes in melanocytes, and increase the melanin synthesis rate in melanocytes over a short period of time.

China’s chronic disease management suffers from problems such as unclear institutional function， insufficient information technology application， and weak regulation support. On the basis of current chronic disease management condition in China， this paper proposes to apply the concept of “people-centered” integrated health management to community chronic disease management and discusses the content and procedure of establishing an integrated community-based chronic disease management model driven by massive databases. The model innovatively combines technology integration， data integration and service integration， and can accurately and efficiently realize the "people-centered" full-course health management of various chronic diseases. Shanghai has provided integrated community-based chronic disease management service for 1.98 million citizens through applying this model. The model warrants further effectiveness and economic evaluation. This study provides precious experience for the development of chronic disease prevention and treatment in China.

The policy implementation model of G. C. Edwards was used to analyze the public policy health impact assessment in Zhejiang province, and summarize its practice and existing problems in four aspects of policy implementation standards, policy resources, policy executors′ intention and management organization structure, so as to provide reference for promoting the national health impact assessment pilot work. The analysis results showed that Zhejiang province has initially established the public policy health impact assessment mechanism and achieved phased results, but there were still some problems, including the imperfection of policy content and implementation strategy, the inadequacy of leadership decision-making and top-level design, the difference in attitude, understanding and implementation preference of policy implementation subjects, and the ambiguity of the authority and responsibility system of each department in cooperation. In order to further promote the smooth development of public policy health impact assessment, Zhejiang province should actively promote the top-level design to strengthen policy support, integrate and optimize policy resources, gradually establish and improve the health governance mechanism of multiple and overall coordination, and promote the high-quality development of public policy health impact assessment by taking cross departmental cooperation as the path of health co-construction.

Objective:To investigate the clinical characteristics and pathogenic mutations of propionic acidemia.Methods:Clinical data of two patients with propionic acidemia admitted to the Obstetrics and Gynecology Hospital of Nanjing Medical University from May 2017 to June 2018 were collected. Genomic DNA was extracted from the peripheral blood of the patients and their parents. Inherited disease panel based on Ion Torrent semiconductor sequencing technology was performed to detect gene mutations, and those with suspected pathogenic mutations were verified by Sanger sequencing. Descriptive statistical analysis was used for data analysis.Results:Case 1 was suspected of sepsis and admitted to the Obstetrics and Gynecology Hospital of Nanjing Medical University due to "drowsiness and milk rejection" on the second day after birth. Tandem mass spectrometry suggested the level of propionyl carnitine and its ratios to acetylcarnitine and free carnitine were increased. Urine gas chromatography-mass spectrometry showed elevated 3-hydroxypropionic acid and methylcitric acid. Genetic analysis revealed that the infant carried c.331C>T (p.R111X)/c.1228C>T (p.R410W) compound heterozygous mutations in the PCCB gene. The infant was diagnosed with propionic acidemia and treated with a special diet with an L-Carnitine supplement but died of sudden coma and vomiting without precipitating factors at three months of age. Case 2 presented with sudden vomiting, drowsiness, and anergia on the admission at five-months old. Tandem mass spectrometry showed increased propionyl carnitine level and its ratios. Compound heterozygous mutations of c.146delG (p.G49EfsX16)/c.1253C>T (p.A418V) in the PCCB gene were identified in the patient, of which c.146delG (p.G49EfsX16) was a de novo mutation and was evaluated as a pathogenic mutation. The patient was on a special diet with an L-Carnitine supplement, but with disobedience. Followed up to the age of three years and eight months, the child was severely underdeveloped. Conclusions:Neonates with clinically suspected sepsis may have propionic acidemia, and tandem mass spectrometry and genetic testing should be performed as soon as possible to confirm or rule out the diagnosis. Further investigations on the pathogenesis and function of the new mutation are still needed.

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light.Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. Conclusion The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.

Objective:To analyze the relationship between both quality and duration of sleep and type 2 diabetes in middle-aged and elderly people in Shanghai.Method:Baseline data was from the '2017 epidemiological survey in Shanghai community residents aged 35 and above on type 2 diabetes’. Restricted cubic splines were used to draw dose-response curves to show the relationship between PSQI score, sleep duration and type 2 diabetes. Logistic regression model was used to analyze the effects of quality and duration of sleep as well as the interaction, on type 2 diabetes.Results:Results showed that the average PSQI score was (4.09±0.10) points, the proportion of poor sleep quality was 12.55% (95% CI: 10.77-14.58) and the average sleep duration was (7.19±0.03) hours. The relationship between PSQI score and diabetes appeared linear, with the relationship between sleep duration and diabetes as U-shaped. After adjusting for confounders, both poor sleep quality (>7 for PSQI score) and short sleep duration (sleep duration <6 hours) significantly increased the risk of type 2 diabetes, with OR=1.17 (95% CI: 1.06-1.30) and 1.20 (95% CI: 1.01-1.41), respectively. From the interaction analysis, data showed that after adjusting for confounders, both sleep duration <6 hours ( OR=1.30, 95% CI: 1.12-1.52) and ≥8 hours ( OR=1.79, 95% CI: 1.04-3.07) with poor sleep quality would increase the risks on diabetes. Conclusion:Both poor sleep quality and short sleep duration were associated with the risk of diabetes, while long sleep duration was only associated with the risk of diabetes when accompanied by poor quality of sleep.

OBJECTIVE: To explore the genetic basis for an infant with early-onset argininemia. METHODS: Potential variant was detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases. Suspected variants were verified by Sanger sequencing. RESULTS: Genetic testing indicated that he has carried c.560+2T>C and c.811T>C compound heterozygous variant of the AGR1 gene, which were inherited from his father and mother, respectively. Among these, c.560+2T>C was suspected to be pathogenic, while c.811T>C was of unknown clinical significance, and both were not reported previously. CONCLUSION The c.560+2T>C and c.811T>C compound heterozygous variants of the AGR1 gene probably underlies the argininemia in this child. Above finding has enriched the variant spectrum of the AGR1 gene.
Arginase ; genetics ; Female ; Genetic Testing ; Humans ; Hyperargininemia ; genetics ; Infant ; Male

Objective To investigate the correlation between 24-h ambulatory blood pressure variability and the overall burden of cerebral small vessel disease (CSVD) in patients with acute ischemic stroke. Methods From March 2016 to December 2017, consecutive patients with acute ischemic stroke admitted to the Department of Neurology, the Affiliated Changshu Hospital of Soochow University were enrolled. The 3. 0 T-MRI was used to assess asymptomatic lacunar infarction, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces within 24 h after admission, and the total CSVD score (0-4) was calculated. 24-h ambulatory blood pressure monitoring was performed 24 to 72 h after admission. Ordinal logistic regression analysis was used to determine the independent correlation between the 24-h ambulatory blood pressure-related index and the total CSVD score. Results A total of 220 patients with acute ischemic stroke were enrolled. The patients were divided into five groups according to the total CSVD score. Univariate analysis showed that there were significant differences in age, homocysteine, the proportion of hypertension, as well as 24 h, daytime and nighttime mean systolic blood pressure (SBP), and coefficient of variation of daytime SBP among the 5 groups (all P < 0. 05). Ordinal logistic regression analysis showed that age (odds ratio [OR] 1. 078, 95％ confidence interval [CI] 1. 051-1. 106; P < 0. 001), 24-h mean SBP (OR 1. 043, 95％ CI 1. 026-1. 060; P < 0. 001), daytime mean SBP (OR 1. 042, 95％ CI 1. 025-1. 059; P < 0. 001), nighttime mean SBP (OR 1. 034, 95％ CI 1. 019-1. 049; P < 0. 001), and coefficient of variation of daytime SBP (OR 1. 129, 95％ CI 1. 052-1. 210; P = 0. 003) were independently correlated with the total CSVD score. Conclusions The elevated 24 h, daytime and nighttime mean SBP levels and coefficient of variation of daytime SBP are independently correlated with the severity of overall CSVD burden in patients with acute ischemic stroke.